Numerous antimicrobial agents have been developed which are effective in treating a variety of pathogenic bacteria. Generally, the functional utility of these agents can be classified into three groups based on their general antimicrobial activity:
(1) drugs which are primarily effective against the gram-positive cocci and bacilli, which tend to have a relatively narrow spectrum of activity, including penicillin G, the semisynthetic penicillinase-resistant penicillins, the macrolides, the lincomycins, vancomycin, and bacitracin; (2) drugs which are primarily effective against the aerobic gram-negative bacilli, which include the aminoglycosides and polymyxins; and (3) relatively broad spectrum drugs which affect both the gram-positive and gram-negative bacilli, including the broad-spectrum penicillins (ampicillin and carbenicillin), the cephalosporins, the tetracyclines, chloroamphenicol, trimethoprin and the sulfonamides.
When the antimicrobial activity of a compound is first tested, patterns of sensitivity and resistance are usually defined. However, the efficacy spectrum can subsequently vary markedly due to the fact that microorganisms can acquire resistance to antimicrobial agents, which allows them to survive in the presence of these antibiotics. In order to overcome this problem, strong impetus exists for the development of new antimicrobial agents.
It has been found that certain novel tetraalkyl ethenylidenebisphosphonates are effective against a broad spectrum of gram-positive and gram-negative microorganisms, such as bacteria, yeasts, viruses, fungi and protozoa, many of which are resistant to the widely used antimicrobials, such as penicillin. These tetraalkyl ethenylidenebisphosphonates can be used to control and eliminate the infectious agents responsible for diseases such as gas gangrene, dental caries, urinary tract infections, gastrointestinal infections, vaginal infections and skin infections. Additionally, the efficacy of these compounds is not significantly affected by the presence of human serum.
Accordingly, it is an object of the present invention to provide certain novel tetraalkyl ethenylidenebisphosphonates which are highly active against a number of pathogenic microorganisms.
A further object of the present invention is to provide pharmaceutical compositions comprising these tetraalkyl ethenylidenebisphosphonates along with a pharmaceutically-acceptable carrier. Still a further object of the present invention is to provide a method of using these tetraalkyl ethenylidenebisphosphonates in the treatment in humans or animals of infectious diseases caused by pathogenic microorganisms. Still a further object of the present invention is to provide a novel one-pot process for the preparation of these tetraalkyl ethenylidenebisphosphonates.